PURPOSE: Gene promoter hypermethylation may have utility as a biomarker for cancer risk in histopathologically benign prostate specimens.
MATERIALS AND METHODS: We conducted a nested case-control study of gene promoter methylation status for five genes (APC, RARB, CCND2, RASSF1, MGMT), measured in benign biopsy specimens from 511 prostate cancer case-control pairs. We estimated the overall and race-stratified risk of subsequent prostate cancer associated with methylation status.
RESULTS: In race-stratified analyses, RARB methylation was associated with higher cancer risk in African Americans (OR=2.18; CI=1.39-3.44). APC methylation was associated with increased risk for high-grade tumors (OR=2.43; CI=1.20-4.90); this risk was higher in African Americans than Whites (OR=3.21 vs. 2.04). In cases, methylation of the RARB and APC genes in benign prostate persisted in matched malignant specimens; in African American cases, combined risk associated with methylation of RARB and APC (OR=3.04; CI=1.44-6.42) was greater than the individual risk of each gene and significantly different from that observed in Whites (OR=1.14; CI=0.56-2.30).
CONCLUSION: We conclude that methylation of the RARB gene in histopathologically benign prostate is associated with statistically significant increased risk for subsequent prostate cancer in African American men. Methylation data on additional genes may improve risk stratification and clinical decision-making algorithms for cancer screening and diagnosis.
Written by:
Tang D, Kryvenko ON, Mitrache N, Do KC, Jankowski M, Chitale DA, Trudeau S, Rundle A, Belinsky SA, Rybicki BA. Are you the author?
Department of Environmental Health Sciences, Columbia University, New York, NY.
Reference: J Urol. 2013 Jan 30. pii: S0022-5347(13)00178-X.
doi: 10.1016/j.juro.2013.01.083
PubMed Abstract
PMID: 23376149
UroToday.com Investigative Urology Section
